Evidence

Organic acids could have provided a more facile and reversible linkage than phosphate in proto-nucleic acid systems.

Glyoxylic acid nucleic acid (gaNA) has a similar geometry to canonical RNA. The enthalpies of formation of both the hemi-acetal and acetal linkages with sugars are more negative than those of its hydrate, and contrast with the positive enthalpies of phosphodiester bond formation in canonical RNA. Dinucleotide linkages can form in this system, linked by either 5’-5’ or 3’-5’ linkages primarily. These linkages are relatively stable at room temperature. Finally, molecular modeling showed minimal perturbation of a double helix containing glyoxylate linkages, which also does not deform with a combination of both R and S linkages. Glyoxylate is a model organic linker that could reasonably have been present on the early Earth.

Authors

Bean, Heather D and Anet, Frank A L and Gould, Ian R and Hud, Nicholas V

Abstract

10.1007/s11084-005-2082-4

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Evidence

Noncanonical nucleobases react with sugars.

As shown here and in previous work, noncanonical nucleobases can undergo reactions readily with sugars. One of these nucleobases, 2,4,6-triaminopyrimidine (TAP), reacts with a variety of sugars under relatively mild conditions to form glycosides. This is in contrast to the canonical nucleobases—adenine, cytosine, guanine, and uracil—which either don’t react with sugars or which do so in very low yields under prebiotic conditions. Furthermore, reactions of TAP with ribose and ribulose give the β-riboside, which is the canonical orientation of the nucleoside in RNA. Overall, this indicates that TAP and other noncanonical nucleobases were much more likely to have reacted with sugars to form nucleosides than the canonical nucleobases.

Authors

Fialho, David M. and Clarke, Kimberly C. and Moore, Megan K. and Schuster, Gary B. and Krishnamurthy, Ramanarayanan and Hud, Nicholas V.

Abstract

The emergence of nucleosides is an important, but poorly understood, element of the origins of life. Weshow that 2,4,6-triaminopyrimidine (TAP), a possible ancestral nucleobase of RNA, is glycosylated in waterby non-ribose sugars in yields comparable to those previously reported for its reaction with ribose. Thevarious sugars surveyed include ketoses and aldoses; tetroses, pentoses, and hexoses and are neutral,anionic, or cationic. Though they vary greatly in structure and properties, the data show that all sugarstested form glycosides with TAP. The structures of the eight TAP glycosides formed with glucose andtwo of its derivatives, glucose-6-phosphate andN-acetylglucosamine, were found to beβ-pyranosideswith the glycosylation site on TAP varying with sugar identity. Our results suggest that prebiotic nucleo-side formation would not have been restricted to ribose if ancestral RNA (or proto-RNA) utilized TAP and/or other proto-nucleobases with similar reactivities, and that the ability to form higher-order structuresmay have influenced proto-RNA monomer selection.

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Evidence

There are plausible prebiotic routes to non-sugar nucleic acids.

A variety of molecules react with nucleobases to form adducts in experiments intended to mimic the early Earth. These spark-discharge experiments like those performed in the seminal Miller-Urey experiments tested various prebiotic nitrogen heterocycles with a suite of electrophiles. A multitude of products were formed, comprising organic nucleobase-functionalized molecules with ionizable or otherwise linkable reactive sites. Potential proto-nucleic acids occupied a wide chemical space on the prebiotic earth and could have accounted for much of the informational potential of early polymers.

Authors

Rodriguez, Laura E and House, Christopher H and Smith, Karen E and Roberts, Melissa R and Callahan, Michael P

Abstract

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth.

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Evidence

Noncanonical nucleobases self-assemble into hexad structures.

Melamine and cyanuric acid molecules assemble in a hexad-like structure in both sheet and stacked forms in aqueous solutions. This demonstrates a possible mechanism by which they could have promoted nucleic acid polymerization. While the canonical nucleobases undergo some assembly (like G-quadruplexes for guanine), it is different in nature, allowing for arbitrarily long stacks that form fibers above a certain concentration. In sum, this property of noncanonical nucleobases promotes their ability to serve as the first recognition units of a proto-nucleic acid.

Authors

Seto, Christopher T and Whitesides, George M

Abstract

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Evidence

Nucleic acid chimeras are less stable than the corresponding homopolymers.

It has been shown previously that Nucleic acid oligomers composed of two different monomer types, ribonucleotides and deoxyribonucleotides, are less stable than homooligomers. Here, authors show that the binding of RNA-TNA chimeric sequences (RTNA) is stronger to a homogenous RNA or TNA oligomer than it is to heterogeneous RTNA. Furthermore, ligation of homogenous RNA ligands is faster and yields more product than ligation of heterogenous RTNA when templated by a RTNA strand. Similar results are found for RNA-DNA chimeras (RDNA). Finally, RDNA can overcome template-product inhibition caused by chimeric sequences. These qualities disfavor the theory that a homogenous nucleic acid system evolved into an entirely different homogeneous nucleic acid system, instead favoring the theory that two independent homogenous systems evolved from an initial heterogenous state.

Authors

Bhowmik, Subhendu and Krishnamurthy, Ramanarayanan

Abstract

Hypotheses of the origins of RNA and DNA are generally centred on the prebiotic synthesis of a pristine system (pre-RNA or RNA), which gives rise to its descendent. However, a lack of specificity in the synthesis of genetic polymers would probably result in chimeric sequences; the roles and fate of such sequences are unknown. Here, we show that chimeras, exemplified by mixed threose nucleic acid (TNA)–RNA and RNA–DNA oligonucleotides, preferentially bind to, and act as templates for, homogeneous TNA, RNA and DNA ligands. The chimeric templates can act as a catalyst that mediates the ligation of oligomers to give homogeneous backbone sequences, and the regeneration of the chimeric templates potentiates a scenario for a possible cross-catalytic cycle with amplification. This process provides a proof-of-principle demonstration of a heterogeneity-to-homogeneity scenario and also gives credence to the idea that DNA could appear concurrently with RNA, instead of being its later descendent.

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